In recent years, infusion apparatus has been developed which can be implanted in the body and remain there for a prolonged period. The apparatus can be refilled with infusate without having to remove the apparatus from the patient's body by injecting additional infusate through a penetrable septum in the apparatus wall located directly under the patient's skin. Examples of infusion apparatus of this general type are disclosed in U.S. Pat. Nos. 3,731,681 and 3,951,147.
In the treatment of some patients such as those afflicted with diabetes, the amount of medication such as insulin infused per unit of time should be adjusted at certain time intervals. This is because the patient's requirements may fluctuate during the day, such fluctuations being caused, for example, by the ingestion of food or by some other transitory condition calling for the administration of a bolus dose of infusate. Some prior implantable infusion devices provide this flexibility, examples being shown in U.S. Pat. Nos. 3,894,538 and 4,077,405.
It has also been proposed to program the daily administration of medication such as insulin. In such apparatus, an infusate injector is moved by a motor drive in accordance with a program in such a way that the desired daily dose is achieved while accounting for fluctuations in the patient's glucose level, temperature and ambient pressure to which the patient is subjected. See, for example, U.S. Pat. No. 4,003,379 and the references cited therein.
The aforesaid implantable infusion apparatus is disadvantaged in one or another of the following respects. Some of the devices of this general type have an excessive energy requirement, either to develop the necessary pressure to dispense the infusate to the patient or to regulate the flow to provide the desired dosages. If the energy requirement is supplied by a battery, that battery has to be replaced or recharged relatively often, requiring, at the very least, penetration of the patient's skin, giving rise to the possibility of infection.
Also, some such prior apparatus only dispense infusate to the patient intermittently or periodically which is disadvantageous in some instances. For example, tests have shown that diabetics should receive a basal dose of insulin which is continuous, with the basal dose being supplemented by so-called bolus doses at certain times of the day, such as at mealtimes. The difference in the basal and bolus flow rates may be several orders of magnitude, and it is quite difficult to achieve proper flow control over that entire range of flow rates. The device disclosed in U.S. Pat. No. 4,140,112 does have the advantage of achieving a continuous dosing of infusate even at very small flow rates. However, that continuous feeding or injection of medication also requires a continuous generation of pressure and consequently a higher requirement of input energy for the electrodes which control infusate flow. Furthermore, that requirement increases substantially when the flow rate of medication is increased.
Also, some such apparatus do not maintain a high enough accuracy of the dose rate with variations in environmental and physiological conditions such as temperature and pressure. Also, some are relatively complicated in their design and control. In other words, they require an excessive number of mechanical components. This renders it impractical to manufacture such devices with the required small size to enable them to be implanted in the patient's body without undue discomfort to the patient.
In general, the prior comparable devices of which we are aware do not take into account all of the physiological concepts and clinical factors involved in the various therapies, particularly diabetes therapy, in connection with which such implantable devices are used. In general, such apparatus should have the following attributes:
1. continuous drug delivery; PA1 2. adjustable infusate flow rate with programmability of rate choices; PA1 3. a large range of flow rate choices; PA1 4. a high accuracy of dose rate, maintained constant with variations in environmental and physiological conditions; PA1 5. simplicity of operation, design and control; PA1 6. low system operating pressures; PA1 7. low infusate operating pressures, thereby providing a low shear in the infusate being delivered; PA1 8. a low power consumption; PA1 9. a long life; PA1 10. the ability for in vivo monitoring and verification of dose rate; PA1 11. a built-in fail-safe mode of operation; and PA1 12. a long refill period.